{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T11:31:46Z","timestamp":1777030306958,"version":"3.51.4"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"17","license":[{"start":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T00:00:00Z","timestamp":1645920000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Refractive errors, particularly myopia, are the most common eye conditions, often leading to serious visual impairment. The age of onset is correlated with the severity of refractive error in adulthood observed in epidemiological and genetic studies and can be used as a proxy in refractive error genetic studies. To further elucidate genetic factors that influence refractive error, we analysed self-reported age of refractive error correction data from the UK Biobank European and perform genome-wide time-to-event analyses on the age of first spectacle wear (AFSW). Genome-wide proportional hazards ratio analyses were conducted in 340\u2009318 European subjects. We subsequently assessed the similarities and differences in the genetic architectures of refractive error correction from different causes. All-cause AFSW was genetically strongly correlated (rg\u2009=\u2009\u22120.68) with spherical equivalent (the measured strength of spectacle lens required to correct the refractive error) and was used as a proxy for refractive error. Time-to-event analyses found genome-wide significant associations at 44 independent genomic loci, many of which (GJD2, LAMA2, etc.) were previously associated with refractive error. We also identified six novel regions associated with AFSW, the most significant of which was on chromosome 17q (P\u2009=\u20093.06 \u00d7 10\u221209 for rs55882072), replicating in an independent dataset. We found that genes associated with AFSW were significantly enriched for expression in central nervous system tissues and were involved in neurogenesis. This work demonstrates the merits of time-to-event study design in the genetic investigation of refractive error and contributes additional knowledge on its genetic risk factors in the general population.<\/jats:p>","DOI":"10.1093\/hmg\/ddac048","type":"journal-article","created":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T12:10:30Z","timestamp":1645704630000},"page":"3012-3019","source":"Crossref","is-referenced-by-count":4,"title":["A genome-wide analysis of 340\u2009318 participants identifies four novel loci associated with the age of first spectacle wear"],"prefix":"10.1093","volume":"31","author":[{"given":"Karina","family":"Patasova","sequence":"first","affiliation":[{"name":"Section of Ophthalmology , School of Life Course Sciences, , London SE1 7EH, UK"},{"name":"King\u2019s College London , School of Life Course Sciences, , London SE1 7EH, UK"},{"name":"Department of Twin Research and Genetic Epidemiology , School of Life Course Sciences, , London SE1 7EH, UK"},{"name":"King\u2019s College London , School of Life Course Sciences, , London SE1 7EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony P","family":"Khawaja","sequence":"additional","affiliation":[{"name":"NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and the UCL Institute of Ophthalmology , London WC1E 6BT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Wojciechowski","sequence":"additional","affiliation":[{"name":"Johns Hopkins Bloomberg School of Public Health , Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1254-0832","authenticated-orcid":false,"given":"Omar A","family":"Mahroo","sequence":"additional","affiliation":[{"name":"Section of Ophthalmology , School of Life Course Sciences, , London SE1 7EH, UK"},{"name":"King\u2019s College London , School of Life Course Sciences, , London SE1 7EH, UK"},{"name":"Department of Twin Research and Genetic Epidemiology , School of Life Course Sciences, , London SE1 7EH, UK"},{"name":"King\u2019s College London , School of Life Course Sciences, , London SE1 7EH, UK"},{"name":"NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and the UCL Institute of Ophthalmology , London WC1E 6BT, UK"},{"name":"Department of Ophthalmology , , London SE1 7EH, UK"},{"name":"St Thomas\u2019 Hospital, Guy\u2019s and St Thomas\u2019 NHS Foundation Trust , , London SE1 7EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Falchi","sequence":"additional","affiliation":[{"name":"Department of Twin Research and Genetic Epidemiology , School of Life Course Sciences, , London SE1 7EH, UK"},{"name":"King\u2019s College London , School of Life Course Sciences, , London SE1 7EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jugnoo S","family":"Rahi","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology , , London WC1E 6BT, UK"},{"name":"University College London , , London WC1E 6BT, UK"},{"name":"UCL Great Ormond Street Hospital Institute of Child Health , London WC1N 1EH, UK"},{"name":"Ulverscroft Vision Research Group , , London WC1N 1EH, UK"},{"name":"University College London , , London WC1N 1EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris J","family":"Hammond","sequence":"additional","affiliation":[{"name":"Section of Ophthalmology , School of Life Course Sciences, , London SE1 7EH, UK"},{"name":"King\u2019s College London , School of Life Course Sciences, , London SE1 7EH, UK"},{"name":"Department of Twin Research and Genetic Epidemiology , School of Life Course Sciences, , London SE1 7EH, UK"},{"name":"King\u2019s College London , School of Life Course Sciences, , London SE1 7EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5752-2510","authenticated-orcid":false,"given":"Pirro G","family":"Hysi","sequence":"additional","affiliation":[{"name":"Section of Ophthalmology , School of Life Course Sciences, , London SE1 7EH, UK"},{"name":"King\u2019s College London , School of Life Course Sciences, , London SE1 7EH, UK"},{"name":"Department of Twin Research and Genetic Epidemiology , School of Life Course Sciences, , London SE1 7EH, UK"},{"name":"King\u2019s College London , School of Life Course Sciences, , London SE1 7EH, UK"},{"name":"UCL Great Ormond Street Hospital Institute of Child Health , London WC1N 1EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the UK Biobank Eye & Vision Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R 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